3-alkyl-4-hydroxymethyl-4-alkyloxazolidines



Unite States Patent 3-ALKYL- 4-HYDROXYMETHYL-4- ALKYLOXAZOLIDINESBernard L. Zenitz, Colonic, N.Y., assignor to Sterling Drug, Inc, NewYork, N.Y., a corporation of Delaware No Drawing. Original applicationMay 2, 1958, Ser. No. 732,436. Divided and this application Oct. 20,1958, Ser. No. 771,695

8 Claims. (Cl. 260307) This invention relates to intermediate used inthe preparation of hydroxylated secondary and tertiary amines, and inparticular it is concerned with intermediate used in the preparation ofN-monoalkyland N,'N-dialkyl- N-[bis(hydroxymethyl)lower-alkyl]-amineswherein the compounds have a total of between eighteen and twentyfourcarbon atoms, inclusive. The invention also concerns acid-addition saltsand methods of preparation of said novel intermediates.

The hydroxylated secondary and tertiary amines prepared from thecompounds of my invention are represented by the following structuralformula:

R RI! wherein R represents a hydrogen atom or an alkyl radical, Rrepresents an alkyl radical, R represents a loweralkyl radical, and thesum of the number of carbon atoms in R, R and R is between fifteen andtwenty-one, inclusive.

The exact nature of the alkyl radicals represented by R, R and R" is notcritical, the only critical feature being the total carbon content ofthe molecule. Thus when R or R are alkyl radicals they can be any ofsuch straight chained or branched chained groups as methyl, ethyl,propyl, isopropyl, butyl, isobutyl, secondary-butyl, tertiary-butyl,pentyl, isopentyl, hexyl, isohexyl, heptyl, octyl, isooctyl, nonyl,decyl, undecyl, dodecyl, tridecyl, tetradecyl, hexadecyl, octadecyl, andthe like. R, in representing a lower-alkyl radical, preferably has fromone to about six carbon atoms, and thus can be any of such radicals asmethyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, andthe like. A particularly preferred class of compounds are those in whichR represents the methyl radical.

The compounds of Formula I are prepared by reacting a Grignard reagent,R"Mg-halide, with a compound having the formula NCE /0 noorn-o-Grn IIIThe compounds of the present invention are represented by Formula III.In the Grignard reagent, R"Mghalide, R represents an alkyl group havingone less carbon atom than the alkyl group R to be introduced RRNC(R)(CHOH) where R and R' can be the 2,964,530 Patented Dec. 13, 1960 R NC(R")(CH OH) 2 where both N-alkyl groups are identical, are produced. If theintermediate III is used, compounds of the formula same or different,are produced. 7

The reaction of R"'Mg-halide with compounds of Formula II or III iscarried out under conditions used for Grignard type reactions, forexample, in anhydrous ether medium.

The intermediates of Formulas II and III are readily prepared bycondensation of formaldehyde with a bishydroxymethyl lower-alkylamine,

or with a secondary amine, R'HNC(R")(CH OH) repectively. The reaction iscarried out by heating the formaldehyde and amine in an inert solventwith means for separating the water formed by the condensation from thereaction mixture.

The structures of the compounds of the invention are established by themode of synthesis and corroborated by chemical analysis.

The invention contemplates the compounds both in the free base form andin the form of acid-addition salts. The preferred acid-addition saltsare those which are appreciably water-soluble so thatthey may beprepared for use in aqueous solution. The oxazolidine of the invention(Formula III) readily form water-soluble salts with conventional acids,such as hydrochloric, hydrobromic, hydriodic, nitric, sulfuric,phosphoric, acetic, propionic, lactic, quinic, phthalic,methanesulfonic, p-toluenesulionic acids, and the like.

The compounds of Formula I having the designated carbon content havebeen found to possess bactericidal activity against such organisms asStaphylococcus aureus, Eberthella typhi, Pseudomonas aeruginosa,Aspergillus niger, and the like.

The bactericidal activity was determined in vitro by measuring theminimal concentration necessary to kill the bacteria in 10 minutes, andit was found that the compounds Were elfective in dilutions ranging from111000 to 1:25,000. They were effective either when dissolved in acidsolution, such as aqueous acetic, propionic, quinic or phthalic acids,or when dispersed in neutral aqueous medium by means of a surface activeagent.

' The compounds are prepared for use by preparing a dilute solution inaqueous acid or a neutral solution containing a surfactant, and appliedto a surface to be disinfected by conventional means such as spraying,swabbing, immersion, and the like.

The oxazolidines of Formula III are useful as intermediates in preparingthe tertiary amines of Formula I, and the oxazolidines, particularlythose in which the sum of the number of carbon atoms in R and R" liesbetween eleven and nineteen, inclusive, are also useful as bactericidalagents.

The following examples will further illustrate the inpropylamine [1; Ris H, R is CH (CH 'R is CH A mixture of 33.15 g. (0.15 mole) of n-decylbromide,

45.4 g. (0.375 mole) of 2-amino-2-methyl-1,3-propanediol and 500 ml. ofn-butyl alcohol was refluxed for ninety hours. The reaction mixture wascooled, concentrated to remove the solvent, and the residue was pouredinto 2 liters of ice water. The aqueous mixture was saturated withsodium chloride and extracted three times with ether. The ether extractswere dried over anhydrous calcium sulfate and concentrated, and theresidue which crystallized upon cooling was recrystallized from 400 ml.of hexane, giving 27.7 g. of N-(n-decyl)-2-methyl-l,3-dihydroxy-2-propylamine, M.P. 45-465 C. (uncorr.). Whenrecrystallized twice from acetone and dried, a sample of the compoundwas obtained in the form of colorless needles, M.P. 45.6-48.2 C. (corn).

Ana'lysis-Calcd. for C H NO C, 68.52; H, 12.74; N, 5.71. Found: C,68.83, 68.90; H, 12.70, 12.50; N, 5.71.

(b) 3 (n decyl) 4 hydroxymethyl 4 methyloxazolidine UH; R is CH (CH R"is CH l.A mixture of 11.1 g. (0.0452 mole) of N-(n-decyl)-2-methyl-1,3-dihydroxy-2-propylamine, 1.41 g. (0.0468 mole) of paraformaldehydeand 100 ml. of dry benzene was refluxed under a water separator forabout two and onehalf hours after which time about 0.8 ml. of water hadbeen collected. The reaction mixture was concentrated to remove thesolvent, and the residue was dissolved in absolute ether and filtered.To the filtrate was added an excess of ethereal hydrogen chloride andthe solution was cooled, wehreupon there separated 12.4 g. ofcrystalline product, M.P. about 70 C. (uncorn). After tworecrystallizations from acetone there was obtained a pure sample of3-(n-decyl)-4-hydroxymethylt-methyloxazolidine in the form of itshydrochloride salt having the M.P. 66.871.4 C. (corn).

Analysis.Calcd. for C H NO HCI: C, 61.30; H, 10.97; Cl, 12.06. Found: C,61.46; H, 11.03; Cl. 11.90.

(c) N (n decyl) N butyl 1,3 dihydroxy 2- methyl-Z-propylamine [1; R isCH (CH R is CH (CH R" is CH can be prepared by causing 3 (n decyl) 4hydroxymethyl 4 methyloxazolidine (prepared from the hydrochloride saltobtained above in part (b) by neutralization with sodium hydroxide andextraction with ether) to react with n-propylmagnesium bromide accordingto the manipulative procedure described below in Example 2, part Example2 (a) N (n dodecyl) 2 methyl 1,3 dihydroxy 2- propylamine [I; R is H, Ris CH (CH R" is CH was prepared from 52.26 g. of n-dodecyl bromide and52.50 g. of 2-amino-2-methyl-1,3-propanediol in 500 ml. of n-butylalcohol according to the manipulative procedure described above inExample 1, part (a). The product was recrystalilzed first from ethanoland then twice from acetone to give 24.75 g. of N-(n-dodecyl)-2-methyl-1,3-dihydroxy-2-propylamine, M.P. 50.8-53.6 C. (corn).

Analysis.--Calcd. for C 'H NO C, 70.28; H, 12.90; N, 5.12. Found: C,70.68; H, 13.02; N, 5.05.

(b) 3 (n dodecyl) 4 hydroxymethyl 4 methyloxazolidine [-III; R is CH (CHR" is CH was prepared from 18.75 g. of N-(n-dodecyl)-2-methyl-1,3-dihydroxy-Z-propylamine and 2.35 g. of paraformaldehyde in 150 ml. ofbenzene according to the manipulative procedure described above inExample 1, part (b). The crude product was dissolved in acetone, thesolution was filtered, and an excess of etheral hydrogen chloride wasadded to the filtrate, followed by additional ether to cause separationof the crystalline product (21.4 g., M.P. 69-72 C. (uncor r.)). Thelatter material was recrystallized from a methanol-ether mixture, thenfrom ethyl acetate and several more times from methanol-ether, and-driedfor eight hours in vacuo at 56 C. togive a sample of3-(n-dodecyl)-4-hydroxymethyl-4-methyloxazolidine in the form of itshydrochloride salt having the M.P. 66.4-70.0 C. (corn).

Analysis.-Calcd. for C17H35N0z.HC1I C, 63.42; H, 11.27; .N, 4.35. Found:C, 63.39; H, 11.32; N, 4.40.

3 (n-- dodecyl) 4 hydroxymethyl 4 methyloxazolidine hydrochloride wasfound to be bactericidally efiective at a dilution of 1:20,000 vs.Staphylococcus aureus and 1:13,000 vs. Eberthella typhi.

(c) N (n dodecyl) N ethyl 1,3 dihydroxy 2- methyl-Z-propylamine [1; R isC H R is 'CH (CH R is CH l.A Grignard reagent was prepared from 3.32 g.(0.137 mole) of magnesium and 19.40 g. (0.137 mole) of methyl iodide in100 ml. of anhydrous ether.

' 3 (n dodecyl) 4 hydroxymethyl 4 methyloxazolidine hydrochloride (10.38g., 0.323 mole) was dissolved in a minimum amount of water and an excessof 50% sodium hydroxide solution was added. The free base was extractedthree times with chloroform, and chloroform extracts were dried bypassage through filter paper and by standing in contact with anhydrouscalcium sulfate. The extracts were concentrated and traces of moisturewere removed by adding dry benzene, boiling ed the benzene and repeatingthe process. The residue was dissolved in ml. of absolute ether, and thesolution was added dropwise to the Grignard reagent over a period ofone-half hour. The reaction mixture was refluxed for four hours and thenhydrolyzed with dilute sulfuric acid, whereupon three layers separated,a top ether layer, a middle layer of the insoluble sulfate salt of thedesired product, and a lower aqueous phase. The ether layer wasseparated and washed with dilute sulfuric acid and with water. Theaqueous washings were combined with the middle layer and the loweraqueous layer, and the whole was extracted five times with chloroform.The chloroform extracts were washed three times with concentratedammonium hydroxide solution, dried over anhydrous calcium sulfate andconcentrated to remove the solvent. The residue was distilled at 134 C.(0.0001 m.) to give 4.80 g. of N(dodecyl)-N-ethyl-1,3-dihydroxy-2-methyl-2 propylamine, n 1.4674.

Analysis.Calcd. for C H NO C, 71.69; H, 13.04; 0, 10.61. Found: C,71.44; H, 12.90; 0, 10.65.

N-(n-dodecyl)-N-ethyl-l,3-dihydroxy 2 methyl -2- propylamine was foundto be bactericidally effective at a dilution of 127200 vs.Staphylococcus aureus and l:l0,700, vs. Eberthella typhi.

By replacement of the methyl iodide in the preceding preparation by amolar equivalent amount of ethyl bromide, n-propyl bromide, isopropylbromide, n-butyl bromide, or n-pentyl bromide, there can be obtained,respectively, N-(n-dodecyl)-N-(n-propyl) 1,3 dihydroxy-Z-methyl-2-propylamine [I; R is CH (CH R is CH (CH R is CHN-(n-dodecyl)-N-(n-butyl)-1, 3-dihydroXy-2-methyl-2-propylamine [1; R isCH-,-(CH R is CH (CH R" is CHN-(n-dodecyl)-N-isobutyl-1,3-dihydroxy-2-methyl 2 propylamine [I; R is(CH CHCH R is CH (CH R" is CH N-(ndodecyl)-N-(n-pentyl) 1,3dihydroxy-Z-methyl-Z-propylamine [I; R is CH (CH R is CH (CH R" is CH orN-(n-dodecyl)-N-(n-hexyl)-1,3-dihydroXy-2- methyl-Z-propylamine [1; R isCH (CH R is CH (CH R" is CH Example 3 (a)N-(n-tetradecyl)-2-methyl-1,S-dihydroxy-Z-propylamine [I; R is H, R isCH (CH R" is CH;,] was prepared from 57.86 g. of n-tetradecyl bromideand 52.50 g. of 2-amino-2-methyl-1,3-propanediol in 500 ml. of n-butylalcohol according to the manipulative procedure described above inExample 1, part (a). The solid product was recrystallized from ethanolto give 37.8 g. of N-(n-tetradecyl)-2-rnethyl-1,3-dihydroxy 2propylarnine, M.P. 5557 C. (uncorr.). The latter material wasrecrystallized several times from acetone and finally from methanol togive a sample having the M.P. 5S.4- 57.6 C. (corn).

Analysis.-Calcd. for C H NO N, 4.65; O, 10.61. Found: N, 4.57; O, 10.40.

N-(n-tetradecyl)-2-methyl-1,3-dihydroxy 2 propylamine was found to bebactericidally effective at a dilu- 5.. tion of 1:25,000 vs.Staphylococcus aureus and 1110,500 Vs. Eberthella typhi.

N-(n-tetradecyl)-2-methyl-1,3-dihydroxy 2 propylamine can be caused toreact with hydrochloric acid, hydrobrornic acid, hydriodic acid, nitricacid, sulfuric acid, phosphoric acid, acetic acid, propionic acid,lactic acid, quinic acid, phthalic acid, methanesulfonic acid, orp-toluenesulfonic acid to give, respectively, the hydrochloride,hydrobromide, hydroiodide, nitrate, sulfate (or bisulfate), phosphate(or acid phosphate), acetate, propionate, lactate, quinate, phthalate,methanesulfonate, or p-toluenesulfonate salts.

By replacement of the 2-amino-2-methyl-1,3-propanediol in the precedingpreparation by a molar equivalent amount of2-amino-2-ethyl-1,3-propanediol, 2-amino-2- (n-propyl)-1,3-propanediol,2-amino-2-isopropyl-1,3-propanediol, 2-amino-2-(n-butyl) 1,3propanediol, or 2-amino-2-(n-pentyl)-l,3-propanediol, there can beobtained, respectively,N-(n-tetradecyl)-2-ethyl-l,3-dihydroxy-Z-propylamine [1; R is H, R is CH(CH R is C H N-(n-tetradecyl)-2-(n-propyl)-1,3-dihydroxy- 2-propylamine[1; R is H, R is CH (CH R" is CH (CH N-(n-tetradecyl)- 2-isopro-pyl 1,3dihydroxy-2-propylamine [1; R is H, R is CH (CH R is (CH CH];N-(n-tetradecyl) 2 (n-butyl)-1,3-dihydroxy-Z-propylamine [1; R is H, Ris CH (CH R" is CH (CH or N-(n-tetradecyl)-2-(n-pentyl)-1,3-di-vN-(n-tetradecyl) 2 methyl-l,3 dihydroxy-2-propylamine can be caused toreact with methyl benzenesulfonate by heating in the presence of sodiumcarbonate in n-butanol solution to give N-(n-tetradecyl)-N-methyl-2-methyl-1,3-dihydroxy-2-propylamine [1; R is CH R is CH3(CH2)I3, R" iSCH3].

(b) 3-(n-tetradecyl)-4-hydroxymethyl-4-mcthyl0xaz0- lidine [III; R is CH(CH R" is CH was prepared from 17.7 g. ofN-(n-tetradecyl)-2-methyl-l,3-dihydroxy- 2-propylamine and 2.02 g. ofparaformaldehyde in 100 ml. of dry benzene according to the manipulativeprocedure described above in Example 1, part (b). There was thusobtained 17.7 g. of3-(n-tetradecyl)-4-hydroxymethyl-4-methyloxazolidine, M. P. 42.0-45.4 C.(corn), when recrystallized from acetone.

Analysis.Calcd. for C H NO N, 4.47; O, 10.21. Found: N, 4.39; O, 10.40.

Byreplacement of the N-(n-tetradecyl)-2-methyl-1,3-dihydroxy-2-propy1amine in the preceding preparation by a molarequivalent amount of N-(n-tetradecyD-Z- ethyl 1,3 dihydroxy 2propylamine, N-(n-tetradecyl) 2 n-propyl) -1,3-dihydroxy-Z-propylamine,N- (ntetradecyl) 2 isopropyl-1,3-dihydroxy-2-propylamine,

N-(n-tetradecyl)-2-(n-butyl)-1,3-dihydroxy 2 propyl amine, orN-(n-tetradecyl)-2-(n-pentyl)-1,3-dihydroxy-2- propylamine, there can beobtained, respectively,3-(ntetradecyl)-4-hydroxymethyl-4-ethyloxazolidine [III; R' isCH3(CH2)13, R" 'is C2H5]; 3-(n-tetradecyl)-4-hydroxymethyl 4 (n propyl)oxazolidine (III; R is CH (CH R" is CH (CH3-(n-tetradecyl)-4-hydroxymethyl 4 isopropyloxazolidine [III; R is CH(CH R is (CH CH]; 3-(n-tetradecyl)-4-hydroxymethyl 4 (nbutyl)oxazolidine [III; R is CH (CH R is CH (CH or 3-(n-tetradecyl)-4-hydroxymethyl 4 (n-pentyl)oxazolidine [111; R is 3( 2)13 is 3( H2)4 (c)N-(n-zetradecyl)-N-ethyl-1,S-dihydroxy-Z-methyl- Z-propylamine [1; R isC H R is CH (CH R" is CH was prepared from 10.55 g. of3-(n-tetradecyl)-4- hydroxymethyl-4-methyloxazolidine and the Grignardreagent prepared from 3.07 g. of magnesium and 17.95 g. of methyl iodideaccording to the manipulative procedure described above in Example 2,part (c). There was thus obtained 5.82 g. ofN-(n-tetradecyl)-N-ethyl-1,3-dihydroxy-Z-methyl-Z-propylamine incrystalline form which when recrystallized twice from ethyl acetate anddried 6 at 25 C. for twenty-four hours had the M.P. 30.3-327.7 C.(corr.).

Analysis.-Calcd. for C H NO C, 72.88; H, 13.15; N, 4.25. Found: C,72.99; H, 12.77; N, 4.22.

N-(n-tetradecyl)-N-ethyl-1,3-dihydroxy 2 methyl-2- propylamine was foundto be bactericidally effective at a dilution of 111,700 vs.Staphylococcus aureus and 1:6800 vs. Eberthella typhi.

By replacement of the 3-(n-tetradecyl)-4-hydroxymethyl-4-methyloxazolidine in the preceding preparation by amolar equivalent amount of3-(n-tetradecyl)-4-hydroxymethyl-4-ethyloxazolidine, 3- (n-tetradecyl)-4-hy-' droxymethyl-4-(n-propyl) -oxazolidine, 3-(n-tetradecyl)-4-hydroxymethyl-4-isopropyl-oxazolidine,3-(n-tetradecyl)-4-hydroxymethyl-4-(n-butyl)-oxazolidine, or3-(ntetradecyl) 4 hydroxymethyl 4 (n pentyl) oxazolidine, there can beobtained, respectively, N-(n-tetradecyl) N ethyl 1,3 dihydroxy 2 ethyl 2propylamine [1; R is C H R is CH (CH R" is C H N (n tetradecyl) N ethyl1,3 dihydroxy 2 (npropyl)-2-propylamine [1; R is C H R is CH (CH R" isCH (CH N-(n-tetradecyl)-N-ethyl-l,3-dihydroXy-2-isopropyl-2-propylamine[I; R is C H R is CH (CH R" is (CH CH]; N-(n-tetradecy1)-N- ethyl 1,3dihydroxy 2 (n butyl) 2 propylamine [1; R is C2H5, R is CH3(CH2)13, R isCH3(CH2)3]; 01' N (n tetradecyl) N ethyl 1,3 dihydroxy 2(npentyl)-Z-propylamine [1; R is C H R is CH (CH R" iS CH (CH Example 4(a) N n-hexadecyl -2-methyl-1 ,3-dihydroxy-2-propylamine [1; R is H, Ris CH (CH R is CH was prepared from 60.6 g. of n-hexadecyl bromide and45.5 g. of 2-amino-2-methyl-1,3-propanedio1 in 500 ml. of nbutyl alcoholaccording to the manipulative procedure described above in Example 1,part (a). The crude product was purified by dissolving it in dilutesulfuric acid, filtering the solution and reprecipitating the productwith ammonium hydroxide, and finally recrystallizing it from ethanol togive 51.8 g. of N-(n-hexadecyl)-2-methyl-1,3- dihydroxy-Z-propylamine,M.P. 54-60 C. (uncorr.). A sample of the compound was recrystallizedagain from ethanol and dried in vacuo for three hours at roomtemperature and five hours at 56 C., M.P. 62.2-64.4 C. (corr.).

Analysis.-Calcd for C H NO C, 72.88; H, 13.15; N, 4.25. Found: C, 73.14;H, 12.90; N, 4.17.

N (n hexadecyl) 2 methyl 1,3 dihydroxy 2- propylamine was found to bebactericidally efiective at a dilution of 1:6300 vs. Staphylococcusaureus and 1:350 vs. Eberthella typhi..

(b) 3-(n-hexadecyl)-4-hydroxymethyl-4-methyl0xaz0lidz'ne [III; R is CH(CH R" is CH Was prepared from 35.0 g. of N-(n-hexadecyl)-2-methyl-1,3-dihydroxy- 2-propylamine and 3.68 g. ofparaformaldehyde in 200 ml. of dry benzene according to the manipulativeprocedure described above in Example 1, part (b). The product wasrecrystallized from acetone to give 30.85 g. of 3 (n hexadecyl) 4hydroxymethyl 4 methyloxazolidine, M.P. 49-52 C. (uncorr.). Two morerecrystallizations from acetone and a final recrystallization frommethanol gave a sample with the M.P. 49.4-52.2 C. (corr.).

Analysis.-Calcd. for C H NO N, 4.10; O, 9.37. Found: N, 4.04; O, 9.30.

(c) N-(n-hexadecyl)-N-ethyZ-I,3-dihydr0xy-2-methyl- Z-propylamine [I; Ris C H R is CH (CH R is CH was prepared from 17.88 g. of3-(n-hexadecyl)-4-.

the oxazolidine instead of ether. The product was re- Example (a)N-(n-octadecyl) -2-methyl-1,3-dihydroxy-2-propylamine [1; R is H, R isCH (CH R" is CH was prepared from 66.6 g. of n-octadecyl bromide and52.5

g. of 2-amino-2-methyl-1,3-propanediol in 500 ml. of nbutyl alcoholaccording to themanipulati-ve procedure described above in Example 1,part (a). The product was recrystallized from methanol to give 61.3 g.of N-(noctadecyl)-2-methyl-1,3-dihydroxy-2-propylamine, M.P. 6768 C.(uncorr.). A sample when recrystallized from methanol and then fromacetone and dried at 56 C. in vacuo had the M.P. 67.7-70.1 C. (corn).

Analysis.-Calcd. for C H NO C, 73.89; H, 13.25; .N, 3.92. Found: C,74.06; H, 12.90; N, 3.84. V

(b) 3-(n-ocradecyl)-4-hydroxymethyZ-4-methyloxazolidine 111; R is CH (CHR" is CH was prepared from 37.9 g. ofN-(n-octadecyl)-2-methyl-1,3-dihydroxy- 2-propylamine and 3.65 g. ofparaformaldehyde in 200 ml. of dry benzene according to themanipulativeprocedure described above in Example 1, part (b). The product wasrecrystallized from acetone to give 37.0 g. of 3 (n octadecyl) 4hydroxymethyl 4 methyloxazolidine, M.P. 54-56 C. (uncorr.). A samplewhen re crystallized from acetone and finally from methanol had the M.P.52.254.6 C. (corn).

Analysis.--Calcd. for C H NO C, 74.74; H, 12.82; N, 3.79. Found: C,74.76; H, 12.70; N, 3.80.

3 (n octadecyl) 4 hydroxymethyl 4 methyloxazolidine was found to bebactericidally effective at a dilution of greater than 1:10,000 vs.Staphylococcus aareus and Eberrhella typhi.

(c) N-(n-octadecyl)-N-ethyl-1,3-dihydroxy-2-methyl-2- propylamine [1; Ris C H R is CH3(CH2)17, R" is CH was prepared from 14.0 g. of3-(n-octadecyl) -4-hydroxymethyl-4-methyloxazolidine and the Grignardreagent prepared from 3.93 g. of magnesium and 23.0 g. of methyl iodideaccording to the manipulative procedure described above in Example 2,part (c). The ether layer from the hydrolyzed reaction mixture wasseparated and extracted with 200 ml. of dilute sulfuric acid and thenthree times with concentrated ammonium hydroxide. The ether solution wasdried over anhydrous calcium sulfate and concentrated to dryness. Theresidue was recrystallized from ethyl acetate to give 8.57 g. ofN-(noctadecyl) N ethyl 1,3 dihydroxy 2 methyl 2- propylamine, M.P. 45-47C. (uncorn). After two recrystallizations from ethyl acetate and a finalrecrystallization from an ethyl acetate-hexane mixture there wasobtained a sample having the M.P. 46.4-49.0 C. (corr.).

Analysis.-Ca-lcd. 'for C H NO C, 74.73; H, 13.32; N, 3.63. Found: C,74.70; H, 13.00; N, 3.62.

Example 6 N,N di(n heptyl) 1,3 dihydroxy 2 methyl 2- propylamine [I; Ris CH (CH R is CH (CH R" is CH ].n-Hexylmagnesium bromide was preparedfrom 41.25 g. (0.25 mole) of n-hexyl bromide and 6.08 i

utes. The reaction mixture was refluxed for four llq lts,

and then there was added 250 ml. of dilute sulfuric acid (equivalent to30 ml. of concentrated sulfuric acid), and the mixture was stirred forfifteen minutes, whereupon threelayers separated. The supernatant etherlayer and the middle layer were washed'twice with dilute sulfuric acid,the ether layer was discarded, and the remainder was made basic withconcentrated ammonium hydroxide. The basic solution was extracted fourtimes with chloroform, and the chloroform extracts were dried andconcentrated. The residue was distilled at 133 C. (0.0002 mm.) to give25.36 g. of N,N-di(n-heptyl)-1,3-dihydroxy- 2-methyl-2-propylamine.

Analysis.-Calcd. for C H NO C, 71.69; H, 13.04; N, 4.65. Found: C,71.66; H, 12.80; N, 4.66.

Alternatively, N,N-di(n-heptyl) 1,3-dihydroxy-2-methyl- 2-propylaminecan be prepared by heating 2-arnino-2- methyl-1,3-propanediol withbetween two and three molar equivalents of n-heptyl bromide in thepresence of sodium carbonate in n-butyl alcohol solution.

By replacement of the n-hexyl bromide in the preceding preparation of amolar equivalent amount of n-octyl bromide or n-nonyl bromide, there canbe obtained, respectively, N,N di(n nonyl) 1,3 dihydroxy 2 methyl-2-propylamine [I; R is CH (CH R is CH (CH R" is CH orN,N-di(n-decyl)-1,3-dihydroxy-2-methyl-2- propylamine [I; R is CH (CH Ris CH (CH R is CH3]- Example 7 N,N di(n -0ctyl) 1,3 dihydroxy 2 methyl2- propylamine [1; R is CH (CH R is CH3(CH2)7, R" is CH was preparedfrom 12.90 g. of S-methyl-l-aza- 3,7-dioxabicyclo[3.3.0loctane and theGrignard reagent prepared from 44.75 g. of n-heptyl bromide and 6.08 g.of magnesium according to the manipulative procedure described above inExample 6. There was thus obtained 26.35 g. ofN,N-di(n-octyl)-1,3-dihydroXy-2-methyl-L propylamine, B.P. 139 C.(0.0003 mm.).

Analysis.-Calcd. for C H NO C, 72.88; H, 13.15; N, 4.25. Found: C,73.10; H, 13.40; N, 4.25.

N,N di(n octyl) 1,3 dihydroxy 2 methyl 2- propylamine was found to bebactericidally effective at a dilution of 1:16,800 vs. Staphylococcusaureas and 123600 vs. Eberthella iyphi.

N,N di(n octyl) 1,3 dihydroxy 2 methyl 2- propylamine can be dissolvedin aqueous acetic, propionic, quinic, or phthalic acids to producesolutions of the acetate, propionate, quinate, or phthalate salts,respectively.

This application is a division of my prior, copending 1 application,Serial No. 732,436, filed May 2, 1958.

wherein R' represents an alkyl radical, R" represents a lower-alkylradical, and the sum of the number of carbon atoms in R and R" isbetween eleven and nineteen, inclusive; and (B) acid-addition saltsthereof.

2. A compound having the formula -NOH 0 HO CHrC-CH2 wherein R representsan alkyl radical having between ten and eighteen carbon atoms,inclusive.

3. 3 (n decyl) 4 hydroxymethyl 4 methyloxazolidine.

4. 3 (n dodecyl) 4 hydroxymethyl 4 methyl oxazolidine.

5. 3 (n tetradecyl) 4 hydroxymethyl 4 methyloxazolidine.

6. 3 (n hexadecyl) 4 hydroxymethyl 4 methyloxazolidine.

7. 3 (n octadecyl) 4 hydroxymethyl 4 methyloxazolidine.

8. The process for preparing a compound having the formula HO CHz-C-GH:

10 wherein R represents an alkyl radical, R" represents a lower-alkylradical, and the sum of the number of carbon atoms in R and R" isbetween eleven and nineteen, inclusive, which comprises heating an aminehavin the for- 5 mula R'NHC(R)(CH OH) and formaldehyde, with means forseparating the water formed in the reaction.

References Cited in the file of this patent Senkus: J. Am. Chem. Soc.,vol. 67, pp. 1515-1519 (1945).

UNITED STATES PATENT OFFICE CERTIFICATION OF CORRECTION Patent Ne.2364,5310 December 13 1960 Bernard L. Zenitz It is hereby certified thaterror appears in the above numbered patent requiring correction and thatthe said Letters Patent should read as corrected below.

Column 8, lines 64 to 69, the formula should appear as shown belowinstead of as in the patent:

R -N CH HOCHg-(f CH CH3 Signed and sealed this 12th day of June 1962.

(SEAL) Attest:

ERNEST W. SWIDER DAVID L. LADD Attesting Officer Commissioner of PatentsUNITED STATES PATENT OFFICE CERTIFICATION OF CORRECTION Patent No,2,964,580 I December 13, 191

Bernard L. Zenitz It is hereby certified that error appears in the abovenumbered patent requiring correction and that the said Letters Patentshould read as corrected below.

Column 3, line 25, for -"wehreupon"-- read me whereupon column 4, line5, for "R read R line 33, for (OgOOO'l rm)" read (0,0001 mm) column 6,line 1, for

"80.,3-327.7 read 30.332,7

Signed and sealed this 9th day of May 1961n (SEAL) Attest:

ERNEST We SWIDER DAVID L, LADD Attesting Officer Commissioner of Patents

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF (A) COMPOUNDS HAVINGTHE FORMULA